A bicistronic adenoviral vector carrying cytosine deaminase and GM-CSF genes significantly improves antitumor immunity and overall survival in colon cancer
dc.authorid | 0000-0003-1631-5739 | |
dc.authorid | 0000-0002-7289-6251 | |
dc.authorid | 0000-0003-0060-259X | |
dc.contributor.author | Akbulut, Hakan | |
dc.contributor.author | Çöleri, Arzu | |
dc.contributor.author | Şahin, Günce | |
dc.contributor.author | Tang, Yucheng | |
dc.contributor.author | Deisseroth, Albert | |
dc.date.accessioned | 2021-06-23T19:49:38Z | |
dc.date.available | 2021-06-23T19:49:38Z | |
dc.date.issued | 2018 | |
dc.department | BAİBÜ, Fen Edebiyat Fakültesi, Biyoloji Bölümü | en_US |
dc.description | Annual Meeting of the American-Association-for-Cancer-Research (AACR) -- APR 14-18, 2018 -- Chicago, IL | en_US |
dc.description.abstract | Background: Combination of cytotoxic treatments with immunotherapeutic agents seem more efficacious than using either strategy alone. Oncolytic viral vectors carrying immunostimulatory genes like GM-CSF have emerged as treatment options in various tumors. Previously, we have shown that combination of suicide gene therapy either with GM-CSF or vector-induced dendritic cells has significant anti-tumor efficacy. In the current study, we aimed to combine the cytotoxic effect of the suicide gene cytosine deaminase and the immunostimulatory effect of granulocyte macrophage colony stimulating factor in a single vector construct. Methods: We have constructed a bicistronic adenoviral vector carrying cytosine deaminase (CD) and granulocyte macrophage-colony stimulating factor (GM-CSF) genes combined with an IRES element and driven by CMV promoter (Ad-CMV-CDiresGMCSF). We tested the in vitro efficacy of the vector in various tumor cell lines and in a mouse model of colon cancer. Results: Our bicistronic vector Ad-CMV-CDiresGMCSF showed significant in-vitro cytotoxic effects on tumor cell lines similar to the vector carrying CD gene alone when 5-FC added. Likewise, the GM-CSF producing efficacy of the bicistronic vector was comparable to the vector carrying GM-CSF gene alone. In the syngeneic colon cancer model, the bicistronic vector carrying CD and GM-CSF genes yielded significant tumor shrinkage and overall survival when compared to the control suicide vector carrying CD gene alone. Accordingly, anti-tumor immune response parameters including CTL assay and immune cell infiltration of tumor tissue were significantly improved in the Ad-CMV-CDiresGMCSF vector treated group (p<0.01). Conclusions: The Ad-CMV-CDiresGMCSF vector construct suggests a potential for the treatment of established tumors by inducing significant tumor killing and tumor-specific immune response. | en_US |
dc.description.sponsorship | Amer Assoc Canc Res | en_US |
dc.identifier.doi | 10.1158/1538-7445.AM2018-5911 | |
dc.identifier.issn | 0008-5472 | |
dc.identifier.issn | 1538-7445 | |
dc.identifier.issue | 13 | en_US |
dc.identifier.uri | https://doi.org/10.1158/1538-7445.AM2018-5911 | |
dc.identifier.uri | https://hdl.handle.net/20.500.12491/9568 | |
dc.identifier.volume | 78 | en_US |
dc.identifier.wos | WOS:000468819505325 | en_US |
dc.identifier.wosquality | Q1 | en_US |
dc.indekslendigikaynak | Web of Science | en_US |
dc.institutionauthor | Şahin, Günce | |
dc.language.iso | en | en_US |
dc.publisher | Amer Assoc Cancer Research | en_US |
dc.relation.ispartof | Cancer Research | en_US |
dc.relation.publicationcategory | Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı | en_US |
dc.rights | info:eu-repo/semantics/openAccess | en_US |
dc.subject | Cytosine Deaminase | en_US |
dc.subject | GM-CSF Genes | |
dc.subject | Bicistronic Adenoviral Vector | |
dc.subject | Colon Cancer | |
dc.title | A bicistronic adenoviral vector carrying cytosine deaminase and GM-CSF genes significantly improves antitumor immunity and overall survival in colon cancer | en_US |
dc.type | Article | en_US |